Nephrotoxic and ischemic insults to the kidney lead to acute renal failure and most often manifest as acute tubular necrosis. Recovery of renal function after acute renal failure is dependent on the replacement of necrotic tubular cells with functional tubular epithelium. In addition, a pronounced proliferative response of the glomerular and peritubular capillary endothelium is observed after ischemic injury. The absence or reduction of epithelial and endothelial regeneration may predispose a patient to tubulointerstitial renal scarring and chronic renal disease. The origin of newly generated renal cells is primarily undefined, but by analogy to other organs, organ-specific pluripotent cells (i.e., renal stem cells) have been suggested as precursors of new cells. However, the identification of adult renal progenitor cells is lacking. Bussolati et al, American J. of Pathology, 166: 545-555, 2005.
Evidence is not conclusive to demonstrate the isolation and culture of renal progenitor cells. Nonetheless a few laboratories have made some attempts to identify and isolate such cells. For example, a study in rodents showed that the renal papilla is a niche for adult kidney stem cells. Further experimentation demonstrated that isolated renal papillary cells possess some degree of multipotential differentiation and when injected directly into the renal cortex, they engraft into the kidney parenchyma. These results suggest that the renal papilla is a niche for a population of kidney progenitor cells involved in kidney maintenance and repair. However, the existence of this progenitor niche in human kidneys remains to be determined. Oliver et al., J. of Clinical Investigation, 114: 795-804, 2004. PCT International Application No. WO2005/021738.
Putative human progenitor cells were isolated from renal tissue of cadaveric kidneys. Isolation of these cells was based on magnetic bead cell separation targeting the surface marker CD133. Further experimentation showed that renal-derived CD133+ cells have the capacity to expand in culture and differentiate in vitro into epithelial or endothelial cells. Upon implantation into SCID mice, CD133+ cells formed tubular structures that expressed renal epithelial markers. Additionally, intravenous injection into mice with glycerol-induced tubulonecrosis, CD133+ cells migrated and integrated into injured kidney tissue. Bussolati et al, American J. of Pathology, 166: 545-555, 2005. These data indicate that progenitor cells are present in human kidney tissue and they might play a role in renal repair. However, the resident population of CD133+ cells in adult kidney tissue is very low and therefore impractical for allogeneic-based cell therapy. A recent approach to identify organ-specific stem cells utilized isolation methods based on the ability of progenitor cells to efflux Hoechst 33342 dye. Cells demonstrating this ability have been termed SP (side-population) cells and have shown varying degrees of stem cell characteristics. Studies have shown that the renal interstitium of rodent kidneys contains SP cells. In addition, kidney SP cells were infused into mice with acute renal failure. Hishikawa et al., J. of Cell Biology, 169: 921-928, 2005. These cells appeared to migrate to the interstitial space and play a role in repair of the damaged renal tissue. However, the existence of SP cells in human kidney tissue remains to be determined. A need exists in the art for an improved source of mammalian or human kidney-derived cells for use in cellular therapy that can be isolated from normal mammalian or human kidney tissue and grown in cell culture.